This project will explore a new paradigm for neural control of breathing which suggests an important role for learning and memory in the central integration of respiratory-related afferent inputs and resultant optimization of respiratory output. The proposed research is motivated by three major recent discoveries: a) in-vitro studies which revealed certain forms of synaptic plasticity in brainstem respiratory-related regions; b) in-vivo studies which demonstrated corresponding forms of nonassociative learning in respiratory pattern generation; and c) modeling studies which suggested learning and memory as useful neural strategies in the optimal regulation of respiratory pattern. The primary objective of the proposed investigation is to obtain direct electrophysiological and pharmacological evidence of learning and memory in specific brainstem nuclei that would bridge the gap between the in-vitro, in-vivo and modeling data as well as elucidate the functional significance of such neural strategies. The specific aims are to discern the following forms of learning and memory in vivo: 1) plasticity of vagal "pump cells" in the nucleus tractus solitarius (NTS); 2) plasticity of carotid chemoafferent input to NTS cells; 3) plasticity in pontine respiratory-related regions. The unit recordings of evoked neuronal activities in these brainstem regions will be compared with corresponding adaptations in the vagal Hering-Breuer reflex and carotid chemoreflex before and after various pharmacological interventions and brainstem lesions in vivo. The results will shed light on the mechanisms of adaptive neural control of breathing in healthy states as well as the neural strategies toward the minimization of the risks of apnea and apneusis in various acute or chronic obstructive and restrictive lung diseases.